Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 7 of 645 for:    Russian Federation | Chile

A Study Of PF-05280014 [Trastuzumab-Pfizer] Or Herceptin® [Trastuzumab-EU] Plus Paclitaxel In HER2 Positive First Line Metastatic Breast Cancer Treatment (REFLECTIONS B327-02)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01989676
Recruitment Status : Active, not recruiting
First Posted : November 21, 2013
Results First Posted : January 23, 2018
Last Update Posted : August 13, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Metastatic Breast Cancer
Interventions Biological: PF-05280014
Drug: Paclitaxel
Biological: Herceptin®
Enrollment 707
Recruitment Details A total of 707 subjects were randomized to the study. Of these, 5 patients were randomized but did not receive study drug.
Pre-assignment Details Participants who fulfilled the inclusion/exclusion criteria were randomly assigned to 1 of the 2 treatments of this study.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until at least Week 33 of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability. Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Period Title: Overall Study
Started 349 [1] 353 [2]
Completed 11 6
Not Completed 338 347
Reason Not Completed
Ongoing at data cutoff             279             279
Discontinued             59             68
[1]
Treated (352 randomized)
[2]
Treated (355 randomized)
Arm/Group Title PF-05280014 Trastuzumab-EU Total
Hide Arm/Group Description Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until at least Week 33 of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability. Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability. Total of all reporting groups
Overall Number of Baseline Participants 349 353 702
Hide Baseline Analysis Population Description
Baseline Analysis Population was based on the Safety Population, which was defined as all participants who were randomized and treated with study drug.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 349 participants 353 participants 702 participants
<18 0 0 0
18 to 64 283 292 575
65 to 84 66 60 126
≥85 0 1 1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 349 participants 353 participants 702 participants
Female
349
 100.0%
353
 100.0%
702
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population
Hide Description ORR was defined as the percentage of participants who achieved complete response (CR, complete disappearance of all target lesions with the exception of nodal disease; all target nodes must have decreased to normal size [short axis <10 mm]) or partial response (PR, ≥30% decrease from Baseline of the sum of diameters of all target measurable lesions; the short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions) by Week 25 of the study and confirmed on a follow-up assessment (Week 33±14 days), based on the assessments of the central radiology review in accordance with RECIST 1.1.
Time Frame From the date of randomization until the cutoff date of 24 August 2016 when all participants had either completed the Week 33 tumor assessment or discontinued study drug earlier than the Week 33 visit.
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study drug.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants with HER2-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Overall Number of Participants Analyzed 352 355
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
62.5
(57.2 to 67.6)
66.5
(61.3 to 71.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-05280014, Trastuzumab-EU
Comments RR and associated 95% CI are unstratified and based on the Miettinen and Nurminen method.
Type of Statistical Test Non-Inferiority
Comments The hypothesis to be tested in this study was that the risk ratio of ORR of PF-05280014 versus that of trastuzumab-EU by Week 25 (±14 days) was within a pre-specified margin of 0.80 to 1.25.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.940
Confidence Interval (2-Sided) 95%
0.842 to 1.049
Estimation Comments [Not Specified]
2.Secondary Outcome
Title One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population
Hide Description One (1)-year PFS rate was analyzed based on the time from date of randomization to first documentation of progressive disease (PD), or death due to any cause in the absence of documented PD, based on the assessments of the central radiology review in accordance with RECIST 1.1. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method. The 95% CI for the hazard ratio was based on the Cox’s proportional hazards model.
Time Frame From the date of randomization until 378 days post-randomization as of the cutoff date of 24 August 2016.
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study drug.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants with HER2-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Overall Number of Participants Analyzed 352 355
Median (95% Confidence Interval)
Unit of Measure: Months
12.16
(11.89 to 13.40)
12.22 [1] 
(11.83 to NA)
[1]
There were insufficient events to estimate the upper bound of the 95% CI.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-05280014, Trastuzumab-EU
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.691
Comments 1-sided log-rank test was used to compare the PFS distribution between the two treatment groups and was stratified by Prior Trastuzumab Exposure (Yes/No) and Estrogen Receptor (ER) Status (ER positive vs. ER negative).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.83 to 1.37
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Duration of Response (DOR) Per Central Radiology Assessments: ITT Population
Hide Description DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of PD, or to death due to any cause in the absence of documented PD, based on the assessments of the central radiology review in accordance with RECIST 1.1. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method. The 95% CI for the hazard ratio was based on the Cox’s proportional hazards model.
Time Frame From the date of randomization until 378 days post-randomization as of the cutoff date of 24 August 2016.
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study drug.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants with HER2-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Overall Number of Participants Analyzed 352 355
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
10.61 [2] 
(10.22 to NA)
[1]
There were insufficient events to estimate the median progression-free time.
[2]
There were insufficient events to estimate the upper bound of the 95% CI.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-05280014, Trastuzumab-EU
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.661
Comments 1-sided log-rank test was used to compare the DOR distribution between the two treatment groups and was stratified by Prior Trastuzumab Exposure (Yes/No) and ER Status (ER positive vs. ER negative).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.08
Confidence Interval (2-Sided) 95%
0.75 to 1.56
Estimation Comments [Not Specified]
4.Secondary Outcome
Title One-year Survival Rate: ITT Population
Hide Description One-year survival rate was analyzed based on the time from date of randomization to the date of death due to any cause while the participant was on the study. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method. The 95% CI for the hazard ratio was based on the Cox’s proportional hazards model.
Time Frame From the date of randomization until 378 days post-randomization as of the cutoff date of 24 August 2016.
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all participants who were randomized to study drug.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants with HER2-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Overall Number of Participants Analyzed 352 355
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
There were insufficient events to estimate the median time to event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PF-05280014, Trastuzumab-EU
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.581
Comments 1-sided log-rank test was used to compare the OS distribution between the two treatment groups and was stratified by prior trastuzumab exposure (Yes/No) and ER status (ER positive vs. ER negative)
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 1.048
Confidence Interval (2-Sided) 95%
0.669 to 1.642
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Serum Peak (1 Hour Post End of Infusion) Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population
Hide Description Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific enzyme-linked immuno-sorbent assay (ELISA).
Time Frame Available peak PK concentration data collected at Cycle 1, Day 1 and Cycle 5, Day 1 as of the data cutoff date of 24 August 2016
Hide Outcome Measure Data
Hide Analysis Population Description
PK population was used for analysis, including all participants receiving PF-05280014 or trastuzumab-EU and had no major protocol deviations that influenced PK assessments, and had at least 1 post dose concentration measurement. “Number of participant analyzed” refers to number of participants with measured PK concentrations for each visit.
Arm/Group Title PF-05280014
Hide Arm/Group Description:
Participants with HER2-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Overall Number of Participants Analyzed 349
Median (Full Range)
Unit of Measure: µg/mL
Cycle 1 Day 1 Number Analyzed 267 participants
90.50
(0 to 246)
Cycle 5 Day 1 Number Analyzed 205 participants
95.6
(0 to 435)
6.Secondary Outcome
Title Serum Peak (1 Hour Post End of Infusion) Concentration of Trastuzumab-EU at Selected Cycles: PK Population
Hide Description Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.
Time Frame Available peak PK concentration data collected at Cycle 1, Day 1 and Cycle 5, Day 1 as of the data cutoff date of 24 August 2016
Hide Outcome Measure Data
Hide Analysis Population Description
PK population was used for analysis, including all participants receiving PF-05280014 or trastuzumab-EU and had no major protocol deviations that influenced PK assessments, and had at least 1 post dose concentration measurement. “Number of participant analyzed” refers to number of participants with measured PK concentrations for each visit.
Arm/Group Title Trastuzumab-EU
Hide Arm/Group Description:
Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Overall Number of Participants Analyzed 353
Median (Full Range)
Unit of Measure: µg/mL
Cycle 1 Day 1 Number Analyzed 259 participants
90.80
(0 to 273)
Cycle 5 Day 1 Number Analyzed 220 participants
94.35
(8.96 to 353)
7.Secondary Outcome
Title Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population
Hide Description Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific ELISA.
Time Frame Available trough concentrations collected from Cycle 1, Day 1 to Cycle 17, Day 1 as of the data cutoff date of 24 August 2016, except the EOT visit and unplanned records.
Hide Outcome Measure Data
Hide Analysis Population Description
PK population was used for analysis, including all participants receiving PF-05280014 or trastuzumab-EU and had no major protocol deviations that influenced PK assessments, and had at least 1 post dose concentration measurement. “Number of participant analyzed” refers to number of participants with measured PK concentrations for each visit.
Arm/Group Title PF-05280014
Hide Arm/Group Description:
Participants with HER2-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Overall Number of Participants Analyzed 349
Median (Full Range)
Unit of Measure: µg/mL
Cycle 1 Day 1 Number Analyzed 349 participants
0
(0 to 123)
Cycle 1 Day 8 Number Analyzed 339 participants
27.9
(0 to 91.5)
Cycle 3 Day 1 Number Analyzed 309 participants
48.2
(0 to 110)
Cycle 4 Day 1 Number Analyzed 304 participants
53.5
(0 to 150)
Cycle 5 Day 1 Number Analyzed 289 participants
57.0
(0 to 182)
Cycle 5 Day 8 Number Analyzed 277 participants
57.4
(9.85 to 174)
Cycle 7 Day 1 Number Analyzed 266 participants
60.8
(0 to 152)
Cycle 8 Day 1 Number Analyzed 255 participants
62.2
(0 to 140)
Cycle 11 Day 1 Number Analyzed 212 participants
54.4
(0 to 148)
Cycle 14 Day 1 Number Analyzed 153 participants
50.9
(0 to 169)
Cycle 17 Day 1 Number Analyzed 106 participants
49.15
(0 to 131)
8.Secondary Outcome
Title Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population
Hide Description Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.
Time Frame Available trough concentrations collected from Cycle 1, Day 1 to Cycle 17, Day 1 as of the data cutoff date of 24 August 2016, except the EOT visit and unplanned records.
Hide Outcome Measure Data
Hide Analysis Population Description
PK population was used for analysis, including all participants receiving PF-05280014 or trastuzumab-EU and had no major protocol deviations that influenced PK assessments, and had at least 1 post dose concentration measurement. “Number of participant analyzed” refers to number of participants with measured PK concentrations for each visit.
Arm/Group Title Trastuzumab-EU
Hide Arm/Group Description:
Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Overall Number of Participants Analyzed 353
Median (Full Range)
Unit of Measure: µg/mL
Cycle 1 Day 1 Number Analyzed 348 participants
0
(0 to 98)
Cycle 1 Day 8 Number Analyzed 340 participants
29.8
(0 to 101)
Cycle 3 Day 1 Number Analyzed 319 participants
50.4
(1.74 to 171)
Cycle 4 Day 1 Number Analyzed 316 participants
54.35
(0 to 148)
Cycle 5 Day 1 Number Analyzed 303 participants
60.0
(0 to 244)
Cycle 5 Day 8 Number Analyzed 287 participants
61.2
(4.64 to 150)
Cycle 7 Day 1 Number Analyzed 275 participants
62.9
(1.93 to 340)
Cycle 8 Day 1 Number Analyzed 261 participants
65.6
(0.69 to 155)
Cycle 11 Day 1 Number Analyzed 215 participants
58.7
(1.52 to 251)
Cycle 14 Day 1 Number Analyzed 142 participants
55.1
(4.68 to 187)
Cycle 17 Day 1 Number Analyzed 101 participants
50.6
(15 to 126)
9.Secondary Outcome
Title Anti-Drug Antibodies (ADA) Incidence: Safety Population
Hide Description Two sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) immunoassays, 1 for detecting antibodies against PF-05280014 and the other for detecting antibodies against trastuzumab, were used to analyze ADA samples. Serum samples were first screened for ADA. Any samples that were positive in the screening assay were further analyzed to confirm the positive result and determine the antibody titers. All samples were taken prior to dosing. The number of participants with a positive sample (titer≥1.0) is provided.
Time Frame Available data from Baseline through Cycle 17, Day 1 as of the data cutoff date of 24 August 2016, except the EOT visit and unplanned records.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was used for analysis, including all participants who received at least 1 dose of study drug. “Number of participants analyzed” refers to number of participants included in the evaluated for ADA at each visit.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants with HER2-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Overall Number of Participants Analyzed 349 353
Measure Type: Number
Unit of Measure: Participants
Cycle 1 Day 1 (prior to treatment) Number Analyzed 349 participants 350 participants
30 14
Cycle 3 Day 1 Number Analyzed 308 participants 321 participants
0 0
Cycle 5 Day 1 Number Analyzed 287 participants 303 participants
0 0
Cycle 8 Day 1 Number Analyzed 253 participants 263 participants
0 0
Cycle 11 Day 1 Number Analyzed 218 participants 222 participants
0 0
Cycle 14 Day 1 Number Analyzed 160 participants 147 participants
0 0
Cycle 17 Day 1 Number Analyzed 107 participants 105 participants
0 1
Overall Number Analyzed 323 participants 331 participants
0 1
10.Secondary Outcome
Title Neutralizing Antibodies (Nab) Incidence at Cycle 1 Day 1 Prior to Treatment: Safety Population
Hide Description Human serum samples testing positive for the presence of ADA (anti-PF-05280014 or anti-trastuzumab-EU) were analyzed for the presence or absence of NAb (neutralizing anti-PF-05280014 or neutralizing anti-trastuzumab-EU antibodies) following a tiered approach using screening and titer determination. All samples at baseline (prior to treatment) or post-treatment were taken prior to dosing. All participants with the exception of 1 participant in the trastuzumab-EU group tested negative for ADA (titer <1.00) from Cycle 1, Day 1 post-treatment through Cycle 17, Day 1. The corresponding NAb result for this Cycle 17, Day 1 ADA positive sample was not yet available; thus, not reported. The number of participants at Baseline (prior to treatment) with a positive NAb sample (titer≥1.48) is provided.
Time Frame Available data from Baseline to Cycle 17, Day 1 as of the data cutoff date of 24 August 2016, except the EOT visit and unplanned records.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population was used for analysis, including all participants who received at least 1 dose of study drug. “Number of participant analyzed” refers to number of participants included in the evaluated for ADA at each visit.
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description:
Participants with HER2-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Overall Number of Participants Analyzed 349 350
Measure Type: Number
Unit of Measure: Participants
16 8
Time Frame Adverse events (AEs) and serious AEs (SAEs) were reported from the time the participant had taken at least 1 dose of study drug and the time of informed consent, respectively, through 70 days after the last dose of study drug.
Adverse Event Reporting Description Incidence of treatment emergent AEs/SAEs was comparable across treatment groups, and defined as AEs occurring from first dose of study drug (or any pre-existing event that worsened in severity after dosing) through 70 days after the last dose of study drug.
 
Arm/Group Title PF-05280014 Trastuzumab-EU
Hide Arm/Group Description Participants with HER2-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability. Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until at least Week 33 of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
All-Cause Mortality
PF-05280014 Trastuzumab-EU
Affected / at Risk (%) Affected / at Risk (%)
Total   16/349 (4.58%)   24/353 (6.80%) 
Show Serious Adverse Events Hide Serious Adverse Events
PF-05280014 Trastuzumab-EU
Affected / at Risk (%) Affected / at Risk (%)
Total   51/349 (14.61%)   54/353 (15.30%) 
Blood and lymphatic system disorders     
Anaemia  1  3/349 (0.86%)  1/353 (0.28%) 
Leukopenia  1  1/349 (0.29%)  1/353 (0.28%) 
Neutropenia  1  3/349 (0.86%)  1/353 (0.28%) 
Thrombocytopenia  1  1/349 (0.29%)  1/353 (0.28%) 
Cardiac disorders     
Atrial fibrillation  1  2/349 (0.57%)  0/353 (0.00%) 
Cardiac arrest  1  0/349 (0.00%)  1/353 (0.28%) 
Cardiac failure  1  0/349 (0.00%)  3/353 (0.85%) 
Cardiac failure acute  1  0/349 (0.00%)  1/353 (0.28%) 
Cardio-respiratory arrest  1  2/349 (0.57%)  0/353 (0.00%) 
Cardiovascular insufficiency  1  0/349 (0.00%)  1/353 (0.28%) 
Pericardial effusion  1  1/349 (0.29%)  0/353 (0.00%) 
Ear and labyrinth disorders     
Vertigo  1  1/349 (0.29%)  0/353 (0.00%) 
Eye disorders     
Macular degeneration  1  1/349 (0.29%)  0/353 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  1/349 (0.29%)  1/353 (0.28%) 
Duodenal ulcer haemorrhage  1  0/349 (0.00%)  1/353 (0.28%) 
Dyspepsia  1  0/349 (0.00%)  1/353 (0.28%) 
Proctalgia  1  1/349 (0.29%)  0/353 (0.00%) 
Small intestinal obstruction  1  1/349 (0.29%)  0/353 (0.00%) 
General disorders     
Cyst rupture  1  1/349 (0.29%)  0/353 (0.00%) 
Death  1  0/349 (0.00%)  1/353 (0.28%) 
Disease progression  1  12/349 (3.44%)  12/353 (3.40%) 
Fatigue  1  1/349 (0.29%)  1/353 (0.28%) 
Pyrexia  1  0/349 (0.00%)  3/353 (0.85%) 
Hepatobiliary disorders     
Cholecystitis  1  1/349 (0.29%)  0/353 (0.00%) 
Immune system disorders     
Drug hypersensitivity  1  1/349 (0.29%)  0/353 (0.00%) 
Hypersensitivity  1  1/349 (0.29%)  0/353 (0.00%) 
Infections and infestations     
Bacteraemia  1  1/349 (0.29%)  0/353 (0.00%) 
Cellulitis  1  1/349 (0.29%)  4/353 (1.13%) 
Cystitis  1  1/349 (0.29%)  0/353 (0.00%) 
Device related infection  1  1/349 (0.29%)  0/353 (0.00%) 
Device related sepsis  1  0/349 (0.00%)  1/353 (0.28%) 
Lower respiratory tract infection  1  0/349 (0.00%)  1/353 (0.28%) 
Mastitis  1  1/349 (0.29%)  0/353 (0.00%) 
Osteomyelitis  1  1/349 (0.29%)  0/353 (0.00%) 
Peritonitis  1  1/349 (0.29%)  0/353 (0.00%) 
Pneumonia  1  4/349 (1.15%)  3/353 (0.85%) 
Respiratory tract infection  1  0/349 (0.00%)  1/353 (0.28%) 
Sepsis  1  0/349 (0.00%)  2/353 (0.57%) 
Septic shock  1  1/349 (0.29%)  0/353 (0.00%) 
Staphylococcal sepsis  1  0/349 (0.00%)  1/353 (0.28%) 
Urinary tract infection  1  1/349 (0.29%)  2/353 (0.57%) 
Wound infection  1  1/349 (0.29%)  0/353 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  0/349 (0.00%)  1/353 (0.28%) 
Infusion related reaction  1  1/349 (0.29%)  1/353 (0.28%) 
Injury  1  0/349 (0.00%)  1/353 (0.28%) 
Laceration  1  0/349 (0.00%)  1/353 (0.28%) 
Spinal compression fracture  1  1/349 (0.29%)  1/353 (0.28%) 
Investigations     
Ejection fraction decreased  1  0/349 (0.00%)  2/353 (0.57%) 
Metabolism and nutrition disorders     
Dehydration  1  0/349 (0.00%)  1/353 (0.28%) 
Hyperglycaemia  1  2/349 (0.57%)  0/353 (0.00%) 
Hypernatraemia  1  1/349 (0.29%)  0/353 (0.00%) 
Hypokalaemia  1  4/349 (1.15%)  0/353 (0.00%) 
Tumour lysis syndrome  1  0/349 (0.00%)  1/353 (0.28%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/349 (0.00%)  1/353 (0.28%) 
Pathological fracture  1  1/349 (0.29%)  0/353 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant pleural effusion  1  2/349 (0.57%)  0/353 (0.00%) 
Ovarian germ cell teratoma benign  1  1/349 (0.29%)  0/353 (0.00%) 
Rectal cancer  1  1/349 (0.29%)  0/353 (0.00%) 
Uterine leiomyoma  1  0/349 (0.00%)  1/353 (0.28%) 
Nervous system disorders     
Cerebral infarction  1  0/349 (0.00%)  1/353 (0.28%) 
Intracranial venous sinus thrombosis  1  1/349 (0.29%)  0/353 (0.00%) 
Ischaemic stroke  1  0/349 (0.00%)  2/353 (0.57%) 
Neuropathy peripheral  1  2/349 (0.57%)  0/353 (0.00%) 
Vocal cord paralysis  1  1/349 (0.29%)  0/353 (0.00%) 
Psychiatric disorders     
Affective disorder  1  0/349 (0.00%)  1/353 (0.28%) 
Suicide attempt  1  1/349 (0.29%)  0/353 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  1/349 (0.29%)  1/353 (0.28%) 
Hydronephrosis  1  0/349 (0.00%)  1/353 (0.28%) 
Reproductive system and breast disorders     
Endometrial hyperplasia  1  0/349 (0.00%)  2/353 (0.57%) 
Metrorrhagia  1  1/349 (0.29%)  0/353 (0.00%) 
Uterine prolapse  1  1/349 (0.29%)  0/353 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  0/349 (0.00%)  1/353 (0.28%) 
Alveolitis allergic  1  1/349 (0.29%)  0/353 (0.00%) 
Bronchospasm  1  1/349 (0.29%)  0/353 (0.00%) 
Chronic obstructive pulmonary disease  1  1/349 (0.29%)  0/353 (0.00%) 
Pneumonia aspiration  1  0/349 (0.00%)  1/353 (0.28%) 
Pneumonitis  1  1/349 (0.29%)  0/353 (0.00%) 
Pulmonary embolism  1  5/349 (1.43%)  2/353 (0.57%) 
Pulmonary oedema  1  2/349 (0.57%)  0/353 (0.00%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  0/349 (0.00%)  1/353 (0.28%) 
Dermatitis contact  1  0/349 (0.00%)  1/353 (0.28%) 
Vascular disorders     
Deep vein thrombosis  1  2/349 (0.57%)  0/353 (0.00%) 
Embolism  1  0/349 (0.00%)  1/353 (0.28%) 
Hypertension  1  0/349 (0.00%)  1/353 (0.28%) 
Hypovolaemic shock  1  0/349 (0.00%)  1/353 (0.28%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PF-05280014 Trastuzumab-EU
Affected / at Risk (%) Affected / at Risk (%)
Total   327/349 (93.70%)   331/353 (93.77%) 
Blood and lymphatic system disorders     
Anaemia  1  117/349 (33.52%)  129/353 (36.54%) 
Leukopenia  1  33/349 (9.46%)  40/353 (11.33%) 
Neutropenia  1  95/349 (27.22%)  90/353 (25.50%) 
Gastrointestinal disorders     
Abdominal pain  1  11/349 (3.15%)  28/353 (7.93%) 
Constipation  1  20/349 (5.73%)  26/353 (7.37%) 
Diarrhoea  1  56/349 (16.05%)  65/353 (18.41%) 
Nausea  1  54/349 (15.47%)  63/353 (17.85%) 
Stomatitis  1  23/349 (6.59%)  12/353 (3.40%) 
Vomiting  1  26/349 (7.45%)  24/353 (6.80%) 
General disorders     
Asthenia  1  50/349 (14.33%)  43/353 (12.18%) 
Fatigue  1  42/349 (12.03%)  49/353 (13.88%) 
Oedema peripheral  1  23/349 (6.59%)  41/353 (11.61%) 
Pyrexia  1  39/349 (11.17%)  26/353 (7.37%) 
Infections and infestations     
Respiratory tract infection viral  1  20/349 (5.73%)  11/353 (3.12%) 
Upper respiratory tract infection  1  30/349 (8.60%)  40/353 (11.33%) 
Injury, poisoning and procedural complications     
Infusion related reaction  1  33/349 (9.46%)  29/353 (8.22%) 
Investigations     
Alanine aminotransferase increased  1  29/349 (8.31%)  41/353 (11.61%) 
Aspartate aminotransferase increased  1  25/349 (7.16%)  26/353 (7.37%) 
Blood alkaline phosphatase increased  1  16/349 (4.58%)  24/353 (6.80%) 
Ejection fraction decreased  1  30/349 (8.60%)  34/353 (9.63%) 
Weight increased  1  15/349 (4.30%)  20/353 (5.67%) 
Metabolism and nutrition disorders     
Decreased appetite  1  21/349 (6.02%)  15/353 (4.25%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  39/349 (11.17%)  35/353 (9.92%) 
Back pain  1  13/349 (3.72%)  29/353 (8.22%) 
Bone pain  1  19/349 (5.44%)  12/353 (3.40%) 
Myalgia  1  21/349 (6.02%)  33/353 (9.35%) 
Pain in extremity  1  19/349 (5.44%)  19/353 (5.38%) 
Nervous system disorders     
Dizziness  1  30/349 (8.60%)  15/353 (4.25%) 
Headache  1  40/349 (11.46%)  51/353 (14.45%) 
Neuropathy peripheral  1  29/349 (8.31%)  33/353 (9.35%) 
Peripheral sensory neuropathy  1  93/349 (26.65%)  83/353 (23.51%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  29/349 (8.31%)  29/353 (8.22%) 
Dyspnoea  1  19/349 (5.44%)  18/353 (5.10%) 
Epistaxis  1  15/349 (4.30%)  22/353 (6.23%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  189/349 (54.15%)  184/353 (52.12%) 
Pruritus  1  11/349 (3.15%)  18/353 (5.10%) 
Rash  1  24/349 (6.88%)  24/353 (6.80%) 
Vascular disorders     
Hypertension  1  34/349 (9.74%)  26/353 (7.37%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01989676     History of Changes
Other Study ID Numbers: B3271002
REFLECTIONS B327-02
2013-001352-34 ( EudraCT Number )
B3271002 ( Other Identifier: Alias Study Number )
First Submitted: October 28, 2013
First Posted: November 21, 2013
Results First Submitted: September 13, 2017
Results First Posted: January 23, 2018
Last Update Posted: August 13, 2019